Continuous wave (CW) spectrophotometers have been widely used to determine in vivo concentration of an optically absorbing pigment (e.g., hemoglobin, oxyhemoglobin) in biological tissue. The CW spectrophotometers, for example, in pulse oximetry introduce light into a finger or the ear lobe to measure the light attenuation and then evaluate the concentration based on the Beer Lambert equation or modified Beer Lambert absorbance equation. The Beer Lambert equation (1) describes the relationship between the concentration of an absorbent constituent (C), the extinction coefficient (xcex5), the photon migration pathlength  less than L greater than , and the attenuated light intensity (I/Io).                                           log            ⁡                          [                              I                /                                  I                  0                                            ]                                            ⟨            L            ⟩                          =                  ∑                                    ε              i                        ⁢                          C              i                                                          (        1        )            
However, direct application of the Beer Lambert equation poses several problems. Since the tissue structure and physiology vary significantly, the optical pathlength of migrating photons also varies significantly and can not be simply determined from geometrical position of a source and detector. In addition, the photon migration pathlength itself is a function of the relative concentration of absorbing constituents. As a result, the pathlength through an organ with high blood hemoglobin concentration, for example, will be different from the same with a low blood hemoglobin concentration. Furthermore, the pathlength is frequently dependent upon the wavelength of the light since the absorption coefficient of many tissue constituents is wavelength dependent. One solution to this problem is to determine xcex5, C, and  less than L greater than  at the same time, but this is not possible with the pulse oximeters known previously.
Furthermore, for quantitative measurement of tissue of a small volume (e.g., a finger) photon escape introduces a significant error since the photons escaped from the tissue are counted as absorbed. Other errors may occur due to irregular coupling of light to the examined tissue or varying relative geometry of the input and detection ports.
The time resolved (TRS-pulse) and phase modulation (PMS) spectrophotometers can measure the average pathlength of migrating photons directly, but the proper quantitation of the time resolved or frequency resolved spectra can be performed only when the spectra are collected at a relatively large source-detector separation. This separation is difficult to achieve for a small volume of tissue such as the earlobe, a finger or a biopsy tissue.
Therefore, there is a need for a optical coupler used with a spectrophotometric system and method that quantitatively examines a relatively small volume of biological tissue.
The invention features a spectrophotometric system for examination of a relatively small volume of biological tissue of interest using visible or infra-red radiation.
According to one aspect of the invention, a spectrophotometric system for examination of a relatively small object of interest (e.g., biological tissue, organic or inorganic substance in a solid, liquid or gaseous state) using visible or infra-red radiation introduced to a path passing through the object. The. system includes a spectrophotometer with an optical input port adapted to introduce radiation into the object and an optical detection port adapted to detect radiation that has migrated through a path in the object, photon escape preventing means arranged around the relatively small object of interest and adapted to limit escape of the introduced photons outside the object, and processing means adapted to determine an optical property of the object based on the changes between the introduced and the detected radiation.
According to another aspect of the invention, a system for examination of a relatively small volume of biological tissue of interest using visible or infra-red radiation includes a spectrophotometer with a light source adapted to introduce radiation at an optical input port, a detector adapted to detect radiation that has migrated through a path from the input port to an optical detection port, and a processor adapted to evaluate changes between the introduced and the detected radiation. The system also includes an optical medium of a relatively large volume, forming photon preventing means, having selectable scattering and absorptive properties, positioning means adapted to locate the biological tissue of interest into the migration path to create a tissue-medium optical path, the optical medium substantially limiting escape of photons from the tissue-medium optical path, and processing means adapted to determine a physiological property of the tissue based on the detected optical property of the tissue-medium optical path and the scattering or absorptive properties of the optical medium.
Preferred embodiments of these aspects of the invention include one or more of the following features.
The photon escape preventing means include an optical medium of a selectable optical property surrounding the object. The selectable optical property is an absorption or scattering coefficient.
The photon escape preventing means include an optical medium surrounding the object; the medium has at least one optical property substantially matched to the optical property of the object.
The spectrophotometer is a continuous wave spectrophotometer (CWS) as described in PCT applications WO 92/20273 and PCT/US95/15666, a phase modulation spectroscopic unit (PMS) as described in U.S. Pat. Nos. 4,972,331, 5,187,672, or a PCT application WO 94/21173, time resolved spectroscopic (TRS) unit as described in U.S. Pat. Nos. 5,119,815 or 5,386,827 or a PCT application WO 94/22361, or a phased array system as described in WO 93/25145, all of which are incorporated by reference as if set forth in their entireties herein.
The determined physiological property is the hemoglobin saturation, the concentration of an enzyme or the concentration of a tissue substance such as glucose.
The system performs a single measurement or a continuous, time-dependent monitoring of the selected physiological property.
The above-described system operates by introducing into the object, surrounded by the photon escape preventing means, electromagnetic radiation of a selected wavelength and detecting radiation that has migrated in the object from the input port to the optical detection port. The system determines an optical property of the object based on the changes between the introduced and the detected radiation. In addition, different photon escape preventing means having a surrounding optical medium with the optical property comparable to the optical property of the object may be selected. Then, the system measures again the optical property of the object. The measurements may be repeated iteratively until the optical property of the surrounding medium is substantially matched to the optical property of the object.
According to another important aspect, the invention is an optical coupling system for non-invasively monitoring a region of living tissue. The coupling system includes an excitation (input) port positionable at the tissue and adapted to introduce optical radiation into the monitored tissue, a first light guide defining an excitation channel for conveying the radiation from a source to the excitation port, and a detection port, positionable at the tissue, adapted to receive radiation that has migrated in the monitored tissue from the excitation port to the detection port. The detection port has a detection area larger than a input area of the excitation port. Connected to the detection port is a detecting light guide, for conveying the radiation from the detection port to an optical detector. The coupling system also includes optical matching fluid contained within a flexible optically transparent bag and disposed partially around the monitored tissue and the excitation and detection ports.
Preferred embodiments of this aspect of the invention includes one or more of the following features.
The optical coupling system may include multiple excitation (input) ports positionable at the tissue and adapted to introduce radiation of the source into the monitored tissue, and multiple light guides, each defining an excitation channel for conveying the radiation from the source to the corresponding excitation port.
The optical coupling system may also include multiple detection ports positionable at the tissue and adapted to receive radiation that has migrated in the monitored tissue, and multiple detecting light guides each connected to the corresponding detection port for conveying the radiation from the detection port to at least one optical detector.
The optical matching fluid may be positioned partially between the ports and the monitored tissue. The optical matching fluid may have known scattering or absorptive properties.
The optical coupling system may further include means for changing scattering or absorptive properties of the optical matching fluid and means for calibrating the coupling system by controllably changing scattering or absorptive properties of the optical matching fluid.
According to another important aspect, the invention is an optical coupler for in vivo examination of biological tissue. The optical coupler includes an optical input port of a selected input area positionable on or near the examined tissue, a first light guide optically coupled to the optical input port and constructed to transmit optical radiation of a visible or infra-red wavelength from a source to the optical input port, wherein the optical input port is constructed and arranged to introduce the optical radiation to the examined tissue, and an optical detection port of a selected detection area positionable on or near the examined tissue. The detection port is constructed and arranged to receive radiation that has migrated in the examined tissue from the input port to the detection port. Optically coupled to the detection port is a detector light guide constructed to transmit the radiation from the detection port to an optical detector. The optical coupler also includes optical medium disposed at least partially around the examined tissue and the input and detection ports and constructed to limit escape of, or account for photons escaped from the examined tissue.
According to another important aspect, the invention is an optical coupler for in vivo examination of biological tissue. The optical coupler includes an optical input port of a selected input area directed toward the examined tissue, an optical detection port of a selected detection area directed toward the examined tissue, and optical medium disposed at least partially around the examined tissue and the input and detection ports. The optical medium is also placed between the tissue and the input area of the input port and between the tissue and the detection area of the detection port, and the optical medium exhibits known scattering or absorptive properties. Optically coupled to the optical input port is a first light guide constructed to transmit optical radiation of a visible or infra-red wavelength from a source to the optical input port that is constructed and arranged to introduce the radiation to the optical medium. The optical detection port is constructed and arranged to receive radiation that has migrated in the examined tissue and the optical medium from the input port to the detection port. Optically coupled to the detection port is a detector light guide constructed to transmit the radiation from the detection port to an optical detector.
According to another important aspect, the invention is an optical coupling system for non-invasively monitoring a region of biological tissue. The coupling system includes a source probe made of at least two optical fibers having distal ends positionable directly at the tissue. Each distal end forms an input port constructed to introduce optical radiation into the examined tissue. The fibers have proximal ends constructed and arranged to form at least one coupling port for receiving the radiation from a source. The coupling system also includes a detection probe made of at least one optical fiber having a distal end positionable directly at the tissue. The distal end forms a detection port constructed to receive radiation that has migrated in the examined tissue. The fiber has a proximal end constructed and arranged to form at least one coupling port for conveying the detected radiation to an optical detector.
The optical fibers may include at the input port or at the detection port an optical matching medium arranged to achieve a desired coupling of the radiation.
Preferred embodiments of this aspect of the invention includes one or more of the following features.
The optical medium may have absorptive or scattering properties substantially matched to the absorptive or scattering properties of the examined tissue.
The optical coupler may further include an optical system constructed and arranged to alter controllably absorptive or scattering properties of the optical medium. The system may be adapted to substantially match the absorptive or scattering properties of the optical medium to the absorptive or scattering properties of the examined tissue.
The optical coupler may further include a second input port of a selected input area, and a light guide optically coupled to the second input port. The detection port may be placed symmetrically relative to the first input port and the second input port. The detection port may be arranged in a transmission geometry or in a backscattering geometry relative to the input ports.
The optical coupler may accommodate movable optical ports relative to the examined tissue.
The optical coupler may further include multiple input ports, and multiple light guides optically coupled to the corresponding input ports. The multiple input ports may be arranged to introduce simultaneously radiation of known time varying pattern to form resulting introduced radiation possessing a substantial gradient of photon density in at least one direction. The multiple input ports may form a one dimensional or two dimensional array. The optical detection port may be movable to another location relative to the examined tissue.
The optical coupler may also include multiple detection ports, and multiple detector light guides optically coupled to the corresponding detection ports.
The optical medium may be made of a solid, liquid, or gas. The optical medium may also include solid particles of smooth, spherical surface, or styrofoam. The optical medium may also include a liquid of selectable scattering or absorptive properties such as an intralipid solution. The optical medium may include a pliable solid of selectable scattering or absorptive properties.
The optical coupler may have the detection area of the optical detection port is larger than the input area of said optical input port.
The optical coupler may further include a port for the needle localization procedure or may be arranged for ultrasonic examination of the tissue performed simultaneously with, or subsequently to the optical examination of the tissue. The optical coupler may further include a set of MRI coils arranged to perform an MRI examination of the tissue.
The optical coupler may be disposed on an endoscope, catheter, guidewire or the like for insertion via a body passage, or transcutaneously, to internal tissue. The optical coupler is designed for visual and spectroscopic examination the selected internal tissue. The catheter may include an inflatable balloon that can press the input and detection ports against the tissue selected for spectroscopic examination. The catheter may also include a biopsy attachment for taking a biopsy specimen from a tissue region before or after the spectroscopic examination.
According to another important aspect, the invention is an optical coupler for in vivo examination of biological tissue. The optical coupler includes an optical input port of a first selected area directed toward the examined tissue and a second selected area oppositely oriented to the first area, and an optical detection port of a selected detection area directed toward the examined tissue. The input port is constructed to accept a light beam scanned over the second area and introduce the beam to the tissue at the first area. The optical coupler also includes optical medium disposed at least partially around the examined tissue and the input and detection ports. The optical medium is also placed between the tissue and the input area of the input port and between the tissue and the detection area of the detection port. The optical medium exhibits known scattering or absorptive properties. The optical detection port is constructed and arranged to receive radiation that has migrated in the examined tissue and the optical medium from the input port to the detection port. Optically coupled to the detection port is a detector light guide constructed to transmit the radiation from the detection port to an optical detector.
Preferred embodiments of this aspect of the invention includes one or more of the following features.
The detection area of the optical detection port may include a multiplicity of detection subareas located at a known position of the detection area. Each detection subarea is constructed and arranged to receive radiation that has migrated in the examined tissue and convey the received radiation to a detector.
The optical detector may include an array of semiconducting detectors each receiving light from a corresponding detection subarea via the detector light guide. Thus a time profile of the detected radiation can be measured at the individual locations.
The light beam may be scanned over the input port using a selected pattern relative to a detection sequence accumulated over the detection subareas. Then, by knowing the input and detection locations of the migrating photons, average photon migration paths may be calculated.
In general, the optical coupling system provides an excellent coupling of light to the examined tissue. The coupling system may also substantially prevent escape of photons from the tissue surface and achieve semi-infinite boundary conditions for the introduced radiation. A larger volume of optical medium is usually used for a small tissue size. The optical coupling system also achieves precisely a selected geometry of the input (excitation) ports and the detection ports regardless of the tissue shape or property. The precise geometry is frequently important for proper evaluation of the photon migration patterns measured by the continuous wave (CWS) unit, the phase modulation unit, the TRS unit, or the phased array unit.